Dioxopiperidines



United States Patent DIOXOPIPERIDHN'ES Karl Hoffmann, Binningen, and Eugen Tagmann, Therwil, Switzerland, assignors to Ciba Pharmaceutical Products, Inc., Summit, N. J.

No Drawing. Application February 4, 1954,

Serial No. 408,308 1 1 3 Claims. (Cl. 260281)' This application is a continuation-in-part of our pending application Serial Number 269,896, filed on February 4, 1952, now Patent No. 2,673,205.

The present invention relates to 2:6-dioxo-piperidines of the formula CgHg . i Claims priority, application Switzerland February 13, 1951 wherein R is a hydrogen or a lower alkyl group es pecially a methyl group. p p I g V v These new compounds possess valuable pharmacological properties and may be used as medicaments. They have a pronounced anti-convulsive eflectjespeciall'y ef fective is the 3-p-chlorophenyl-3-ethyl-2:6-dioxo piperi dine. This effect was tested in mice and rats against shocks produced in different ways. Both the electroshock and the shock due to pentamethylenetetrazole were relieved with doses whichare too small to produce general toxic symptoms. Spasms due to strychnine or sound irritation can also be suppressed. 7

According to the invention the specified dioxo-piperidines are obtained when 2-p.-ch1oro-phenyl-2-ethy1- pentane-1:5-diacid or itsfunctionalderivatives by treatment with condensing agents, suchas sulfuric acid, are

converted into its cyclicimides. According to one ,fea-

ture of the invention-the said pentane-hS-diacicl or its functional derivatives such as its halides, are reacted with ammonia or lower alkyl amines. i

The N-unsubstituted dioxo-piperidine obtained accord- J A mixture of 26.5 parts by weight of 2-p-chlorophenyl-Z-ethyl pentane 1,5 diacid monomethyl estermono-nitrile (1), parts by volume of. glacial acetic acid and 3.5 parts by volume of per cent sulfuric acid is heated to l05 C. for 30 minutes and is then.

refluxed for 3-hours. Most of the solvent is distilled [under reduced pressure and the 'residue 'is poured on an ice-water mixture. The precipitate'is collected by filtration; washed with water, dissolved in ether and the ethereal solution 'washed with aqueous sodium ,bicar-.

bonate in {order to tremove acidic contaminants. The

ether-layer is dried over magnesiumsulfate, filtered and v :the solvent removed.

The residue, after recrystallisation from i-propylalcohol, melts at 108-109 'C. and consists of 3-p chloropheny1-3 ethyl-2: 6- dioxo piperidine of the. formula air 4/ lit 5 i A v p p Example 2 To a solution of 2 5.2 parts by weight of 3-p-chlorophenyl-3-ethyl-2:6-dioxo-piperidine in. parts by volume ofdry dioxane there are .addedin anatmos phere of dry nitrogen 5 parts by weight of powdered sodamidea The mixture is' 'refluxed for 2 hours whereupon it is cooled'iand transferred into a pressure bottle mixed with "l8 parts by weight of methyliodide and, after'seal ing the bottle, heatedto 110-.-l20 C. for Shours. To"

the, cooled mixture a few milliliters of methanol are added and the dioxane is distilled underreduced pressure. i The residue is dissolved Iin ether, the ethereal solution is washed with ,dilute sodium bicarbonatesolution and water, dried over magnesiumsulfate andthe solvent is removed; 'The' remaining .oil is distilled in yacuo; "The 1:methyl:3 p-ch1or-phenyl- 2:6-dioxo-piperidineofthefo'rrnula: p

. b0ils, ati13 5"-14 2 C; under 0.17 pressure. 7

i 1, Acompoundf the formula f sisting of hydrogen and methyl.

2. -3-p-chloropheny1-? -ethyl 2 6-dioxo-piperidine.

,wherein R' is aimembe'riselected from thev group con.

ime, p

' I ReferencesiCited in the file ofthis patent V UNITED, STATES PATENTS 2,664,424 Hoffman et 51. :Dec.i2, 1953 I Patented June? 21, 1955 

1. A COMPOUND OF THE FORMULA 